#ASCO21: Takeda fleshes out case for oral EGFR drug with follow-up pivotal data in non-small cell lung cancer
Takeda is looking to carve out a major niche in non-small cell lung cancer with an oral TKI inhibitor targeting a rare but desperate patient population. Now, with the FDA already checking its math, Takeda is unveiling updated data adding even more heft to that drug’s case.
Takeda’s mobocertinib posted a median OS of 24 months at a 14-month follow-up in patients with EGFR Exon20 insertion mutation-positive, metastatic NSCLC who received prior platinum-based chemotherapy, according to follow-up data from a Phase I/II study set to be presented at ASCO in June.
The results follow up topline data presented in January showing mobocertinib hit an ORR of 35% as judged by the trial’s investigators and 28% from an independent data review committee. The drug also showed a median duration of response of 17.5 months — both investigators and the DRC agreed on that figure — and progression-free survival of 7.3 months.
The pooled results show promise for exon 20-positive patients, who make up about 10% of the total EGFR NSCLC population and have a particularly poor prognosis. It’s a small population but one with a high unmet clinical need.
The FDA granted a priority review for the oral drug in that population late last month with a review date set for Oct. 26. The OS data were included in Takeda’s application and will be reviewed as part of the regulatory approval process.
There was one major red flag on mobocertinib’s record in the Phase I/II test — a high rate of severe diarrhea in trial patients, enough so that they instituted a diarrhea management protocol for patients in the Phase I portion of the trial and continued in the Phase II expansion. In all, diarrhea was reported in 91% of all patients with severe side effects, followed by rash at 45%.
Even with the guidelines in place, the vast majority of patients with severe side effects reported diarrhea, likely indicating an even higher rate of diarrhea in patients who didn’t receive the protocol.
When asked to clarify in January the rate of diarrhea in patients prior to those guidelines being put in place, Takeda’s head of oncology Chris Arendt “caution(ed) a little bit in terms of over-interpreting” and said the protocol was designed to be “available to patients and not onerous.” The drugmaker plans to present further details on those guidelines at a later date, Arendt said at the time, and noted that severe diarrhea is common in exon 20-positive patients after chemo.